Alfaxalone Facts

3/1/2020

ALFAXALONE FACTS

Fernando Garcia-Pereira DVM, MS, DACVAA Veterinary Anesthesia Services (VAS)-JAX [email protected]

Characteristics • Neurosteroid in Cyclodextrin • One of the steroid anesthetics found in Saffan®

• Acts on the GABAA receptor – Unconsciousness and muscle relaxation

Cardiovascular Effects • Similar cardiovascular effects to propofol – HR –  or C.O. (dose dependent) –  BP (vasodilation)

Veterinary Anaesthesia and Analgesia, 2008, 35, 451-462 Cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in dogs W Muir, P Lerche, A Wiese, L Nelson, K Pasloske, T Whittem 3

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Cardiovascular Variables

HR MAP Cardiac Index 150 80 200 75 100 Alfaxalone Alfaxalone Alfaxalone 70 100 50 Propofol Propofol Propofol 65 0 60 0

J Am Vet Med Assoc. 2019;254(12):1421-1426 Recovery characteristics of dogs following anesthesia induced with tiletamine- zolazepam, alfaxalone, ketamine-diazepam, or propofol and maintained with isoflurane. Hampton CE, Riebold TW, Mandsager RE. 4

Cardiovascular effects during CRI • Dose dependent cardiovascular and respiratory depression • Similar to propofol

AJVR, 2008, 69(11): 1391-8 Comparison of the anesthetic efficacy and cardiopulmonary effects of continuous rate infusions of alfaxalone-2-hydroxypropyl-beta-cyclodextrin and propofol in dogs Ambros B, Duke-Novakosvski T, Pasloske KS 5

Respiratory Effects • Dose dependent: – Respiratory depression • Hypercapnea is common – Decrease in PaO2 • hypoxemia can occur, oxygen supplementation is advisable – Apnea –MOST COMMON SIDE EFFECT!!! » Always have endotracheal tubes with you and a anesthetic machine ready

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APNEA • Most common side effect independent of route of administration

Neurologic Effects • CNS friendly • Excitation in cats during recovery (IM route) • Longer duration compared to propofol

Br J Anaesth. 1985 Apr;57(4):369-74. Use of a continuous infusion of althesin in neuroanaesthesia. Changes in cerebral blood flow, cerebral metabolism, the EEG and plasma alphaxalone concentration. Bendtsen A, Kruse A, Madsen JB, Astrup J, Rosenørn J, Blatt-Lyon B, Cold GE.

APGAR SCORES Percentage of puppies in each score category within 5 minutes of birth 80% 60% 40% 20% 0% Severe distress Moderate distress No distress Alfaxalone Propofol

Theriogenology, 80 (2013): 850-854 Apgar score after induction of anesthesia for canine cesarean section with alfaxalone versus propofol A. Doebelia, E. Michela, R. Bettschartb, S. Hartnackc, I.M. Reichlera 9

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Theriogenology • Allopregnanolone analog • Potential protective effect in premature fetus when labor is induced by glucocorticoids (Betamethasone)

Neuropharmacology. 2014 Oct;85:342-8. The effects of betamethasone on allopregnanolone concentrations and brain development in preterm fetal sheep. Yawno T, Mortale M, Sutherland AE, et al.

Quality of Anesthesia Recovery • Smooth recovery for propofol and alfaxalone • Poorer with Ketamine/diazepam and Telazol

Note: Alfaxalone half-life is longer than propofol

Doses

• Dose – Cat: 2-5 mg/kg IV 3-5 mg/kg IM – Dog: 1-3 mg/kg IV 1-3 mg/kg IM (limited by volume in large dogs)

Vet Anaesth Analg. 2017 Jul;44(4):794-802 Intramuscular injection of alfaxalone in combination with butorphanol for sedation in cats. Deutsch J, Jolliffe C, Archer E, Leece EA.

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Cardiorespiratory Neurologic • Similar cardiovascular • CNS friendly effects to propofol • Potential protective effect – HR in premature fetus when –  or C.O. (dose labor is induced by dependent) glucocorticoids –  BP (vasodilation) (Betamethasone) • • Dose dependent Excitation in cats during respiratory depression recovery (IM route) • – Apnea after bolus Longer duration compared to propofol

• No difference between the cardiovascular and respiratory effects of propofol and alfaxalone • NO support alfaxalone safer than propofol • Same safety precautions: – Endotracheal tubes, oxygenation, anesthesia machine available and MONITORING!!

Opinion • Can be use interchangeably with propofol • Main advantage: CAN BE GIVEN IM – Great substitute for Ketamine (in cats) • Careful with apnea and overdose during induction (dose dependent hypotension)

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CAPNOMETRY: CLINICAL INTERPRETATION OF VALUES AND WAVEFORMS

Fernando Garcia-Pereira DVM, MS, DACVAA [email protected]

DEFINITION OF CAPNOGRAPHY

• Graphic representation of respiratory CO2 • EtCO2 is the expired pressure of carbon dioxide

• EtCO2 is an approximation of PaCO2

Alveol i

vein PACO2 artery

PvCO2 PaCO2

Capillary 3

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VENTILATION/PERFUSION RATIOS

PACO2= 0 PACO2 = PaCO2

PvCO2 = PaCO2 Hypoperfusion Normal Atelectasis

Mouth Piece ETCO2

Airway

PACO2

PaCO2 5

END TIDAL CO2 – ETCO2

1- PaCO2 ~ PACO2

2- EtCO2 ~ PACO2 EtCO2 EtCO2 ~ PaCO2

P CO = P CO PACO2 A 2 a 2

PaCO2

Normal

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LEARNING ASSESSMENT!!

•Healthy 2 year old Lab recovering from a TPLO. After oxygen is removed SpO2 is low (88%). Differentials? Most likely? Diagnostic planning…

DIFFERENTIALS FOR HYPOXEMIA

• HYPOVENTILATION (>45 mmHg PaCO2) • V/Q mismatch (atelectasis) • Alveolar diffusion barrier • R-L Shunt (vascular anomaly)

• Low inspired oxygen concentration (below 21% of O2)

DIAGNOSTIC PLANNING

HYPOVENTILATION • Check PaCO2 for abnormality • Can use ETCO2 • Can use Blood Gas (BETTER $$$) • Why not try first the ETCO2? • Specially if still intubated • Can still do even if not intubated

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POSSIBILITIES OF ETCO2 VALUES

Higher than Lower than normal Normal normal (Hyperventilation) (Euventilation) (Hypoventilation)

POSSIBILITIES OF ETCO2 VALUES

Lower than normal Normal EtCO2 EtCO2 Higher than But way higher normal But way higher PaO2 But higher PaO2 PaO2

WHAT TO LOOK FOR:

DURING ANESTHESIA (100% O2) DURING RECOVERY (21% O2) • Animal panting with normal • PulseOxi at low 90s or below temperature 90% • Tachycardia and Tachypnea • Animal seems still very sedated • Seems light but at expected or • Potential over use of opioid higher concentration of inhalant (CRI) or recent dose of one • Hypertensive • Obese animal • Non opioid responsive

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FACTORS AFFECTING ETCO2

PROCEDURES PATHOLOGIES • THORACOTOMIES • GDV • LAPAROSCOPIES • RESPIRATORY Dz • TRENDELEMBURG • OBESITY POSITION • CARDIOVASCULAR Dz • SOME ORTHOPEDIC JIGS

APPLICATIONS FOR ETCO2 MONITORING

• CO2 analysis can assess (EtCO2 vs PaCO2) • Ventilation • Metabolism • Cardiovascular status • Equipment/ patient problems

CAPNOMETRY

Equipment Design • Mainstream • Side stream

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MAINSTREAM

• Infrared • Light Absorption • Dissimilar atoms

• Cannot measure O2

MAINSTREAM

Advantages Disadvantages • Less maintenance • Fragile sensor • Less disposable parts • Adds weight on tube • No scavenging • Adds dead space • Fast response time • Longer warm up time • No standard gas • Measure CO2 only

MAINSTREAM

False low Et CO2

Correct

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SIDESTREAM

• Infrared, • Mass Spectrometry • Raman Spectrometry

SIDESTREAM Advantages Disadvantages • Possible multi gas analysis • More disposable parts • Away from patient • Longer response time • Inexpensive and light • Calibration cylinder interface • Scavenging required • Water Trap

CAPNOMETRY BENEFITS

• Proper Intubation • Malfunction • System Integrity • Respiration/Circulation • Rebreathing • Respiratory depression • Change in Metabolic Rate • Best tool during CPR

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CHEMICAL COLORIMETRIC ANALYSIS

• pH sensitive chemical indicator • Useful to check: • Changes color with change in pH • Intubation • Not quantitative!! • Apnea

• Careful with contamination • Careful with low CO2 • Easy Cap II (< 0.5%)

NORMAL CAPNOGRAPH

HYPERCAPNEA

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REBREATHING

CAREFUL WITH SIDESTREAM! TRULY REBREATHING?

AIRWAY OBSTRUCTION

SAMPLING LINE LEAK AND IPPV

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BLOOD LOSS

CAPNOMETRY

• Factors affecting accurate ETCO2 measurement • Ventilation/Perfusion status • Open thorax • Integrity and type of machine • Contamination • Equipment error

CONCLUSION Great tool Careful use • Proper intubation • May underestimate • Apnea PaCO2 • Cardiorespiratory • May require blood gas and metabolic status for true ventilatory assessment (PaCO ) • Equipment integrity 2